Abstract and Introduction

Abstract

Staphylococci are abundant bacteria of the human skin microbiome. Several species, particularly Staphylococcus aureus and Staphylococcus epidermidis, are opportunistic pathogens and cause significant disease. The human skin serves many functions and here we review its role as an antimicrobial barrier and the staphylococcal mechanisms to colonize and counteract the various stresses present in this niche. Successful colonization is achieved using a diversity of adhesins, surface proteins and secreted enzymes to counteract the antimicrobial peptides, enzymes and lipid matrix components present in the acid mantle. Further mechanisms enable these bacteria to overcome osmotic and acid stresses and desiccation in order to survive the exacting demands of an ever-changing landscape.

Introduction

The skin is a vital barrier against infection with many defenses to prevent invasion, yet many organisms thrive within this hostile environment. Resident bacteria of the skin microbiome, including certain species of staphylococci, supplement the barrier function of the epidermis by inhibiting the colonization of skin pathogens such as Staphylococcus aureus through nutrient competition and the production of antimicrobial peptides (AMPs).[1] The importance of the human microbiome in health and disease is increasingly being recognized and is driving efforts to model the community structure of the resident microbiota.[2–5] Such studies highlight the diversity of the resident skin community across the human body over time, between individuals and ages.[3,6–9]

Staphylococci are the most studied of the resident skin flora owing to their ubiquitous colonization of human skin and the wide spectrum of diseases they cause. The dominant Staphylococcus species on skin is S. epidermidis, which is considered to be a universal colonizer and part of a pan-microbiota.[10] Across different body sites a substantial proportion of the skin community comprises coagulase-negative staphylococci (CoNS), including S. hominis, S. haemolyticus, S. saprophyticus, S. capitis, S. warneri, S. simulans and S. cohnii. Coagulase-positive S. aureus is not considered to be part of the natural skin microbiota and nasal decolonization treatments reduce its frequency on skin.[11,12] While most CoNS interactions with skin are likely to be commensal, they can cause opportunistic infections.[13] Staphylococcal diseases range from common skin ailments, such as boils and impetigo, to urinary tract infections and more serious diseases, including postsurgical infections, device-associated disease, toxic shock syndrome and systemic infection.[14]S. aureus colonization has been linked as a risk factor of certain infections, such as bacteremia.[15]

Initial studies of staphylococcal adhesion focused on binding to the extracellular matrix and plasma proteins. More recently, studies have investigated adhesins for human keratinocytes and their ligands. Many receptor interactions are scarcely characterized, including loricrin, desmoglein-1, desmocollin-1 and keratinocyte lipids. Loricrin comprises up to 80% of protein on terminally differentiated keratinocyte cell surfaces, desmoglein-1 and desmocollin-1 are involved in intercellular keratinocyte adhesion, and keratinocyte lipids form an envelope around the terminally differentiated keratinocyte cell surfaces. Alternative acronyms are shown in the adhesin column.

Tables

Box 1. Models of staphylococcal skin colonization.

Many subcutaneous disease models have been described for staphylococci. In addition, there are various, recently described colonization models for normal and diseased skin, including:

Cutaneous colonization by tape-stripping of shaved murine skin

Model uses a stretch plaster for mild or strong tape-stripping of shaved skin to generate defects in the epithelial barrier. The intact epidermis was inoculated with 10 7Staphylococcus aureus [161]. The model was used to assess bioburden and measure the inflammatory response

Pruritic disease model of murine skin

Model generates pruritic dermatitis following the injection of capsaicin that has similarities to atopic dermatitis. Model used for study of inflammatory mediators and filaggrin immunohistochemistry [162]

Allergic immune response model of murine skin

Established the use of human-SCID mice for the study of inflammation responses as a model of atopic dermatitis [163]

Human volar forearm colonization–survival model

Model used for determining comparative survival of an isogenic, unmarked isdA mutant of S. aureus by viable counting of bacteria after inoculation [105]

Murine ear colonization model

Through the application of S. aureus to the ear of BALB/c-nu/nu mice, the role of β-hemolysin in skin colonization was determined [80]

Murine nasal colonization model

This model established temporal studies of S. aureus colonization and was used to differentiate survival of isogenic mutants [164]. Use of loricrin-deficient mice extended the model to demonstrate the role of ClfB binding to squamous epithelial cells [157]

SCID: Severe combined immunodeficiency.

References

Authors and Disclosures

Authors and Disclosures

Financial & competing interests disclosure R Coates and J Moran are supported by BBSRC-Unilever CASE studentships BB/I532161/1 and BB/J500768/1 to MJ Horsburgh. The funders had no role in data collection and analysis, decision to publish or preparation of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Esterification of AFAs to reduce toxicity is mediated by fatty acid-modifying enzyme and this activity is widespread, but not universal, in S. epidermidis , and is present in other staphylococci tested.

Morphological changes, which limit osmotic stress, are proposed to increase desiccation tolerance. The exopolysaccharide, polysaccharide intercellular adhesin, is postulated to aid survival through surface area reduction and regulating water levels.